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Biomedical subjects

S Baba

Publications and source records attributed to S Baba.

At least 145 records · Page 8Linked to original sources

[Extragonadal seminoma with testicular microlithiasis: a case report].

A 43-year-old men presented with left supraclavicular growing mass. Ultrasonography revealed a 31 x 21 mm solid mass with a homogeneous echoic pattern. Lymph node metastasis of some malignant neoplasms was highly suspected. However, whole body evaluation with computed tomographic scan revealed no findings in the primary region. In addition, tumor markers including alpha fetoprotein, human chorionic gonadotropin and carcinoembryonic antigen were within normal limits. Then, extirpation of supraclavicular mass was performed and pathological diagnosis was made as pure seminoma. Evaluation of testicle by ultrasonography revealed a diffuse calcification. However, histological examination of biopsy specimen of testicle revealed no malignancy. The mass was finally diagnosed as extragonadal or "burned-out" pure seminoma. The patient received two courses of Peplomycin, vinblastine and cisplatin (PVP) therapy, and there has been no evidence of recurrence for 34 months.

Adult↗

[Clinical evaluation of biapenem in various infectious diseases].

The clinical usefulness of injectable biapenem (BIPM) was examined for various infectious diseases in the fields of internal medicine, urology, surgery, orthopedics, obstetrics and gynecology, otorhinolaryngology, ophthalmology, dermatology, oral surgery, and plastic surgery. BIPM was administered by intravenous drip infusion at a dose of 150, 300, or 600 mg twice a day. The concentrations in various body fluid and tissues were also examined. 1. In the total enrollment of 256 cases, the numbers subjected to the analyses for clinical efficacy, bacteriological efficacy, side effects and abnormal laboratory findings were 214, 170, 252 and 251 cases, respectively. 2. The clinical efficacy rate was 85.5% (183/214 cases) as a whole, being 2/2 for sepsis, 6/8 for cellulitis and lymphangitis, 76.2% (16/21) for traumatic, operative wound and burn infections, 4/6 for osteomyelitis and arthritis, 92.9% (13/14) for peritonsillar abscess and peritonsillitis, 83.3% (15/18) for chronic lower respiratory tract infection, 7/7 for pneumonia, 83.3% (30/36) for complicated urinary tract infection, 100% (14/14) for cholecystitis and cholangitis, 88.2% (15/17) for peritonitis, 86.5% (32/37) for internal genital infection, 8/9 for pelvic peritonitis, 2/4 for corneal ulcer, orbital infection and panophthalmitis, 1/2 for otitis media, 4/4 for sinustitis, 93.3% (14/15) for osteitis of jaw and cellulitis of mouth floor. The efficacy rate in the poor responders to the pretreatment by other antibiotics was 86.4% (70/81). 3. 300 strains of causative organisms were isolated from 170 cases which contained polymicrobial infections. The elimination rate of causative organisms was 85.3% (256/300 strains), in terms of bacteriological efficacy. 4. Side effects were noted in 11 of 252 cases (4.4%) with 11 events. The signs and symptoms were the skin symptoms (5 cases), gastro-intestinal symptoms (3 cases), interstitial pneumonia (2 cases), and feeling bad (1 case), all of which disappeared during treatment or after the discontinuation of treatment. The abnormal laboratory findings were observed in 31 of 251 cases (12.4%) with 50 events, and major ones were an increase in eosinophils, and elevations of AST, ALT, gamma-GTP and Al-p. 5. The concentrations of BIPM in body fluid and tissues were determined in 46 cases (212 samples) most of which were administered 300 mg of BIPM by intravenous drip infusion for 60 minutes. The concentrations in the sputum within 6 hours after administration were 0.1-2.5 micrograms/g. The maximum concentrations in body fluid and tissues were 0.2-1.8 micrograms/g or ml in the bile, middle ear mucosa, tonsillar tissue, aqueous humor and bone tissues and were 2.0-5.7 micrograms/g or ml in the gallbladder, maxillary sinus mucous membrane, ethmoidal sinus mucous membrane, oral tissues, skin, woman genitals, synovia, joint tissue, and the eschar. The concentrations in the uterine arterial plasma and retroperitoneal fluid were almost similar to those in the cubitl vein plasma. From the above-mentioned results of clinical efficacy, bacteriological efficacy, and safety, injectable BIPM was confirmed to be useful in the treatment of moderate, severe and/or refractory infections in various fields.

Adult↗

hOGG1 Ser326Cys polymorphism and lung cancer susceptibility.

The human homologue of the yeast OGG1 gene, hOGG1, has been cloned, and its genetic structure has been determined. Several polymorphisms in the hOGG1 gene were detected in the Japanese populations, and among them, the Ser-Cys polymorphism at codon 326 has been shown to have a functional difference in complementation of mutant Escherichia coli that is defective in the repair of 8-hydroxyguanine. Activity in the repair of 8-hydroxyguanine is greater in hOGG1-Ser326 protein than in hOGG1(326) protein. Because many environmental carcinogens produce 8-hydroxyguanine residue and mismatching to this modified base potentially causes oncogenic mutations, the capacity to repair these lesions can be involved in cancer susceptibility in human beings. We, therefore, examined allele distributions of the Ser326Cys polymorphism in a case-control study of male lung cancer in Okinawa. The analyses based on 241 cases and 197 hospital controls disclosed the following findings. (a) Those with the Cys/Cys genotype were at an increased risk of squamous cell carcinoma and nonadenocarcinoma compared to those with the Ser/Cys and those with the Ser/Ser genotypes combined. The odds ratios adjusted for age and smoking history were 3.01 (95% confidence interval, 1.33-6.83) and 2.18 (95% confidence interval, 1.05-4.54), respectively. (b) The odds ratios for other histological subtypes of lung cancer or those in total were not significant. Those for Cys/Cys or Ser/Cys genotype against Ser/Ser did not reach statistical significance in any cell type. (c) The distributions of this polymorphism varied for different populations (Chinese, Japanese, Micronesians, Melanesians, Hungarians, and Australian Caucasians), with much less prevalence of Cys allele in the latter three populations. Although our sample size was limited, these results indicate that the Ser326Cys variant may be related to squamous cell lung cancer susceptibility. The Cys/Cys genotype appears to be more susceptible to squamous cell carcinoma, although the risk is less than that previously reported to be associated with the CYP1A1 gene. Further studies are needed to assess the importance of the interpopulation variation to cancer susceptibility.

Adult↗

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent head and neck cancer].

A late phase II clinical study of RP56976 (docetaxel), a new anticancer agent for advanced/recurrent head and neck cancer, was conducted in 29 institutions all over Japan as a multi-institutional cooperative study. Docetaxel was administered by 1 to 2-hour intravenous infusion at a dose of 60 mg/m2 every 3 to 4 weeks. Of 63 patients eligible in this study, 59 were judged as complete cases. Complete response (CR) was observed in 1 patient, partial response (PR) in 13, no change (NC) in 25, and progressive disease (PD) in 20, for an overall response rate of 22.2% (14/63, 95% CI: 12.7-34.5%) in eligible cases, and 23.7% (14/59, 95% CI: 13.6-36.6%) in complete cases. Previously treated patients showed a 17.9% (10/56) response rate, whereas treatment--naive patients showed a 57.1% (4/7) response rate. Among 46 patients who received prior chemotherapy, one CR and 7 PR were observed with a 17.4% response rate. Major hematological toxicities were leucopenia in 95.1% (> or = grade 3, 59.7%) and neutropenia in 90.3% (> or = grade 3, 79.0%). Other severe toxicities (> or = grade 3) included anorexia in 9.7% (6 cases), diarrhea in 3.2% (2 cases), dyspnea in 3.2% (2 cases), and fatigue in 3.2% (2 cases). One patient had a grade 3 interstitial pneumonia; however, symptoms were resolved by the administration of corticosteroids. During this study, one patient died due to multiple organ failure (MOF) caused by disseminated intravascular coagulation (DIC), and this case was reported as a therapy-related death. Based on these results, docetaxel is an active agent for treatment of head and neck cancer.

Adenocarcinoma↗

Anti-tumor and anti-metastatic effects of human-vascular-endothelial-growth-factor-neutralizing antibody on human colon and gastric carcinoma xenotransplanted orthotopically into nude mice.

In order to determine whether the inhibition of vascular-endothelial-growth-factor (VEGF) activity by administration of an immunoneutralizing antibody could suppress tumor growth and metastasis in spontaneous metastatic models of human colon and gastric carcinoma, 4 human carcinoma xenografts, 2 human colon carcinomas (TK4 and TK 13) and 2 gastric carcinomas (MT2 and MT5) were transplanted orthotopically into nude mice. The anti-VEGF antibody (MV833, 100 microg/mouse) or the same volume of saline was administered i.p. on alternative days from day 10 after transplantation. With each of the 4 xenografts, administration of MV833 significantly inhibited not only primary tumor growth but also macroscopic liver metastasis, although the growth rate varied. The inhibitory effect of MV833 on primary tumor growth appeared to have no correlation with the level of VEGF in tumor. Body-weight gain in each treated group was comparable with that in the control group. No toxicity of the antibody was observed. These results suggest that an anti-VEGF antibody can be effective against a wide variety of cancers, and that VEGF may be a possible target for cancer therapy.

Adenocarcinoma↗

Complete sequence and gene organization of the genome of a hyper-thermophilic archaebacterium, Pyrococcus horikoshii OT3.

The complete sequence of the genome of a hyper-thermophilic archaebacterium, Pyrococcus horikoshii OT3, has been determined by assembling the sequences of the physical map-based contigs of fosmid clones and of long polymerase chain reaction (PCR) products which were used for gap-filling. The entire length of the genome was 1,738,505 bp. The authenticity of the entire genome sequence was supported by restriction analysis of long PCR products, which were directly amplified from the genomic DNA. As the potential protein-coding regions, a total of 2061 open reading frames (ORFs) were assigned, and by similarity search against public databases, 406 (19.7%) were related to genes with putative function and 453 (22.0%) to the sequences registered but with unknown function. The remaining 1202 ORFs (58.3%) did not show any significant similarity to the sequences in the databases. Sequence comparison among the assigned ORFs in the genome provided evidence that a considerable number of ORFs were generated by sequence duplication. By similarity search, 11 ORFs were assumed to contain the intein elements. The RNA genes identified were a single 16S-23S rRNA operon, two 5S rRNA genes and 46 tRNA genes including two with the intron structure. All the assigned ORFs and RNA coding regions occupied 91.25% of the whole genome. The data presented in this paper are available on the internet at http:@www.nite.go.jp.

Chromosomes, Archaeal↗

Development of an assay for bioactive insulin.

A method to detect the biological activity of serum insulin has been developed. This method, called a bioactive insulin assay, determines the ability of serum insulin to stimulate the autophosphorylation of insulin receptors in an intact cell system. For this, intact Chinese hamster ovary cells which overexpress the human insulin receptor are treated with serum and then lysed. Autophosphorylation of the insulin receptors is then measured by a two-site immunofluorometric assay using monoclonal anti-insulin receptor antibodies and europium-labeled anti-phosphotyrosine antibodies. The detection limit of this assay is 1 microU/ml of insulin. Dilution and recovery test inter- and intraassay coefficient variations are permissible. The amount of insulin determined by this assay correlated well with the amount of insulin detected by a traditional immunological assay for insulin (r = 0.94, P < 0.001). In the case of a mutant insulin, the insulin from a Wakayama subject, the biologically active insulin was found to constitute 9% of the immunologically reactive insulin. Since this assay specifically measures the amount of biologically active insulin present in serum, it should be particularly useful in monitoring active insulin in patients with various mutant insulins.

Animals↗

Pathophysiological appraisal of a rat model of total hepatic ischemia with an extracorporeal portosystemic shunt.

BACKGROUND: Animal models of total hepatic ischemia (THI) and reperfusion injury are restricted by concomitant splanchnic congestion. This study was performed to determine the requirement suitable for an extracorporeal portosystemic shunt (PSS) to maintain the intestinal integrity in a rat model of THI. MATERIALS AND METHODS: Using a polyethylene tube (0.86 or 1 mm i.d.), PSS was placed between the mesenteric and jugular veins. Comparison was done between THI models with or without PSS and a partial ischemia model with hepatectomy of the nonischemic lobes. Well-tolerated hepatic ischemic period, portal pressure after 10 min of hepatic ischemia, portal endotoxin levels at 1 h after reperfusion, histological features of the small bowel just before reperfusion, and local jejunal and ileal blood hemoglobin oxygen saturation index (ISO2) were compared among the models. RESULTS: Animals without PSS poorly tolerated 30 min of THI. Animals receiving THI with PSS or partial hepatic ischemia tolerated a longer ischemic period (60 min) with a significantly higher small bowel ISO2, lower portal pressure and endotoxin levels (P < 0.01), and less histological damage of the small bowel when compared to those receiving THI without PSS. Portal endotoxin levels after THI with PSS using a 1-mm i.d. tube as well as partial hepatic ischemia were significantly lower than those after THI with PSS using a 0.86-mm i.d. tube. CONCLUSIONS: THI with PSS using a 1-mm i.d. tube was strikingly similar to partial hepatic ischemia in the pathophysiological profile during hepatic ischemia. PSS with a tube 1 mm or more in inner diameter offers pathophysiological advantages in experiments on THI and reperfusion.

Animals↗

Primary dissection of the hepatic artery: report of a case.

Dissecting aneurysms of the hepatic artery are extremely rare. We report herein the case of a 51-year-old man with massive hepatic metastases from rectal carcinoma, who was found incidentally to have a left hepatic artery aneurysm by a preoperative angiography. After replacing the left hepatic artery with a 2-cm segment of long saphenous vein, an extended right lobectomy with partial resection of the left lateral segment for multiple metastases was successfully performed. To prevent thrombus formation at the anastomosis, the Pringle maneuver was not used during dissection of the hepatic parenchyma. Histological examination of the resected specimen showed a dissecting aneurysm of the left hepatic artery, but there were no findings to suggest the etiology of this disease. The patient is currently alive 13 months after his operation without any evidence of further recurrence of the carcinoma. To the best our knowledge, 12 case reports of this anomaly have been documented, but only one of these describes a successful operation. The clinical features and etiology of the hepatic artery aneurysm that develops independent of other vascular diseases are discussed following this case report.

Aortic Dissection↗

Murine cytomegalovirus induces apoptosis in non-infected cells of the developing mouse brain and blocks apoptosis in primary neuronal culture.

Cytomegalovirus (CMV) is the most common cause of congenital infection, resulting in birth defects such as microcephaly. In this study, we found that apoptosis is induced in the developing mouse brain infected with murine cytomegalovirus (MCMV) in an association with neuronal cell loss. With the combination of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique and immunohistochemical staining, 3.8% of the TUNEL-positive cells were double-stained with the antibody to neuron-specific enolase, while none of the TUNEL-positive cells were stained with antibodies to the immediate early and early viral antigens of MCMV. Furthermore, distribution pattern of the TUNEL-positive cells was different from that of viral DNA-positive cells detected by the in situ DNA-DNA hybridization. More than 30% of the TUNEL-positive cells were double-stained with the F4/80 antibody specific for microglia/macrophages, which were sometimes swollen, presumably the consequence of engulfment of the neuronal apoptotic cells. In the primary neuronal cultures, MCMV infection inhibited the induction of apoptosis either by serum deprivation or by glutamate treatment. It was also confirmed by the double-staining method that apoptosis was not induced in the viral-infected neuronal cultures. These results suggest that MCMV infection induces apoptosis in non-infected neuronal cells, presumably by indirect mechanisms, and that apoptotic cells are engulfed by microglia/macrophages. The induction and blocking of neuronal apoptosis by viral infection may be important for morphological and functional brain disorders in the congenital CMV infection.

Animals↗

Localization of the gene responsible for Peutz-Jeghers syndrome within a 6-cM region of chromosome 19p13.3.

Patients with Peutz-Jeghers syndrome (PJS), an autosomal dominant disease characterized by hamartomatous polyposis of the gastrointestinal tract, are thought to be predisposed to malignancies of the digestive tract, genital tract, and other organs. Using microsatellite markers on chromosome 19p, we have closely defined the region containing the gene responsible for this disorder through linkage analysis in seven affected families. The lack of obligate recombinants at two of these loci, D19S883 and D19S878, with maximum LOD scores of 2.88 and 3.75, confirmed the localization of the PJS locus to chromosome 19. Furthermore, haplotype analysis placed the PJS locus within a 6-cM telomeric region of chromosome 19p, between D19S886 and D19S565.

Centromere↗

Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome.

Peutz-Jeghers Syndrome (PJS) is an autosomal dominant hereditary disease characterized by hamartomatous polyposis involving the entire bowel. Recently STK11, a gene bearing a mutation responsible for PJS, was isolated. We investigated the entire coding region of STK11 in 15 unrelated PJS families by the PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) method and PCR-direct sequence analysis, and found nine different, novel mutations among ten of those families. One nonsense mutation and five different frameshift mutations (two families carried the same mutation), all of which would cause truncation of the gene product, were found in seven families; mutations found in five families were clustered within exon 6. Among these five mutations, three occurred at the mononucleotide-repeat region (CCCCCC) of codons 279-281, suggesting that this region is likely to be a mutational hotspot of this gene. One of the remaining three families carried a 3-bp in-frame deletion that would eliminate an asparagine residue within a kinase domain of the product; the other two carried intronic mutations at or adjacent to the consensus dinucleotide sequences of splice-acceptor or -donor sites, which were likely to lead to aberrant splicing.

AMP-Activated Protein Kinase Kinases↗

Surgical management for a malignancy of the digestive organs accompanied with an abdominal aortic aneurysm.

Surgical management of patients with simultaneous coexisting malignancy of the digestive organs and an abdominal aortic aneurysm (AAA) remains controversial. In the five patients who underwent the aneurysmectomy first, no complications developed after an aneurysmectomy and a resection of malignancy could be performed within 4 weeks, whereas postoperative complications after the resection of malignancy developed in two of them. Two patients underwent a one-stage operation, in which one was unable to tolerate the two procedures, and no postoperative complications were seen; however, one patient with cardiac dysfunction who first underwent an aneurysmectomy died 3 months after operation due to cardiac and renal failure. These results indicate that the aneurysmectomy first is preferred, when such patients do not have absolute indications of malignancy or AAA; however, a one-stage operation should be chosen when the patients show a disturbance of key organs.

Adult↗

Development of approximate formula for LDL-chol, LDL-apo B and LDL-chol/LDL-apo B as indices of hyperapobetalipoproteinemia and small dense LDL.

Estimation of LDL-chol and LDL-apo B is useful for the diagnosis of hyperapobetalipoproteinemia (normal LDL-chol with increased LDL-apo B), which is one of the most commonly occurring lipoprotein disorders associated with atherosclerotic cardiovascular diseases. The LDL-chol/LDL-apo B ratio reflects the level of small dense LDL, which is an important risk factor for IHD, CVD and ASO. In order to estimate LDL-apo B and LDL-chol/LDL-apo B ratio from blood chol, TG, HDL-chol and apo B values, we developed a formula for LDL-chol ¿0.94Chol- 0.94HDL-chol - 0.19TG¿, LDL-apo B ¿apo B - 0.09Chol + 0.09HDL-chol-0.08TG¿, and LDL-chol/LDL-apo B [¿0.94Chol-0.94HDL-chol - 0.19TG¿/¿apo B - 0.09Chol + 0.09HDL-chol-0.08TG¿] using ultracentrifugal data from 2179 subjects. These were calculated by the least squares method on the assumption that a certain compositional relationship exists between Chol, TG and apo B in VLDL, IDL and LDL. Friedewald's formula for LDL-chol (Chol - HDL-chol - 0.2TG) includes IDL-chol, but the present new formula theoretically excludes IDL-chol. It suggests a better estimation for the correct LDL-chol. Estimated LDL-apo B is useful for the diagnosis of hyperapobetalipoproteinemia and detection of small dense LDL. Without performing ultracentrifuge, additional information is obtained for the quantitative and qualitative alteration of LDL, such as small dense LDL. The above formulae and a new classification of lipoproteinemia including apo B were applied to the analyses of lipoprotein profiles of subjects with cardiovascular diseases, which were compared with those in the general population. Hyperapobetalipoproteinemia with high TG was observed 2-3 times more frequently in subjects with CAD, MI and ASO than in the Suita population. Lower ratios of LDL-chol/LDL-apo B, reflecting preponderance of small dense LDL, were observed in the above three groups. Type IIb and combined low HDL-chol were also frequent phenotypes in CAD, A-Th and ASO. The present formulae are useful for the detailed analyses of lipoprotein disorders in both qualitative as well as quantitative aspects.

Apolipoproteins B↗

Development of vanadate sensitive human erythrocytes insulin receptor tyrosine phosphatase assay.

The aim of this study was to investigate the effect of sodium orthovanadate on the alterations of human erythrocytes insulin receptor autophosphorylation. Human erythrocytes were incubated with insulin in a cell system and then lysed. The autophosphorylated insulin receptors were measured with the aid of a two-site immunofluorometric assay and using a monoclonal anti-insulin receptor antibody to label the insulin receptors and a monoclonal anti-phosphotyrosine antibody to assess tyrosine phosphorylation. When the erythrocytes were treated with insulin and then reincubated in insulin-free medium, vanadate completely inhibited insulin receptor dephosphorylation, although it had no effect on in vitro receptor autophosphorylation. Thus insulin receptor tyrosine phosphatase activity is postulated to be [% (autophosphorylated insulin receptors with vanadate - autophosphorylated insulin receptors without vanadate)/total insulin receptors] under overall steady conditions in a cell system. Using this assay, the insulin receptor tyrosine phosphatase activities of 25 control and 32 diabetic subjects were studied. There was no significant difference in insulin receptor tyrosine phosphatase activity between control subjects and diabetic subjects (0.173 +/- 0.062 vs 0.209 - +/- 0.057 autophosphorylated insulin receptors units/insulin receptors units). The assay used in this study requires only 0.6 ml of whole blood, and so should be a useful tool for detecting patients who are insulin-resistant due to abnormal insulin receptor tyrosine phosphatase activity.

Animals↗